Diagnostic assays for the detection of various substances ("analytes") in clinical specimens (e.g. plasma, serum, urine) are well known. These clinical diagnostic assays can be divided generally into two systems: heterogeneous and homogeneous systems. Heterogeneous systems, for example ELISA (enzyme linked immunosorbent assay), typically involve the use of an analyte- or antibody-linked solid phase for signal generation and require the separation and washing of the solid phase to reduce non-specific binding to the solid phase or background signal in assay measurements. In contrast, homogenous systems, such as the COBAS.RTM. FP and COBAS.RTM. OnLine (Roche Diagnostic Systems, Inc., Branchburg, N.J.), TDx.RTM. FP (Abbott Laboratories, North Chicago, Ill.), EMIT.TM. (Syva Co., Palo Alto, Calif.), and CEDIA.RTM. (Microgenics Corp., Concord, Calif.), utilize only liquid reagents and the signal is generated directly from the mixture of reagents without any separation procedure. Because of their simplicity, homogeneous assays may be fully automated.
It is also known to include various additives in the washing buffer of heterogeneous immunoassays to enhance the performance of the assay. For example, U.S. Pat. No. 5,393,659 discloses the use of a water-soluble polymer containing carboxyl groups to improve the sensitivity of ELISA assays. These "enhancing" additives typically do not participate in the immunochemical reaction itself but rather facilitate the washing efficiency and reduce the non-specific binding to the solid phase thereby decreasing the background signal (i.e., a heterogenous system). These additives may also enhance the minimal readable concentration of analyte, i.e. improve the sensitivity of the assay. See, e.g., U.S. Pat. No. 5,393,659.
Turning to the analytes that are detected by immunochemical assays, aminoglycoside antibiotics are known to exhibit high potency and to have a broad-spectrum bactericidal action against both Gram-negative and Gram-positive organisms. However, they are also known to have a narrow therapeutic index, making their use hazardous, particularly in patients with impaired renal function. See M. Jolley, et al., Clin. Chem. 27(7):1190-1197 (1981); U.S. Pat. No. 5,079,234. Thus, patients being treated with aminoglycoside antibiotics are closely monitored for concentration of these drugs in their serum. Id. Because of the high toxicity potential of these drugs, there is also a continuing effort to improve the performance and sensitivity of known assays for aminoglycoside antibiotics.